The objectives of this application are to continue our studies on the control of proliferation and differentiation in human, non- Hodgkin's B cell lymphomas (NHL-B). Since we have shown that BCGF-like lymphokine growth factors are important molecules in controlling growth factors in these tumors, particularly in the most aggressive forms of NHL-B, it is of particular importance to establish the biochemical nature of the autocrine BCGF-like molecules, which we believe are responsible for the autonomous rapid cell growth characteristic of these lymphomas. The specific aims of this proposal seek to: (1) characterize the nature of the BCGF-like autocrine growth factor molecules in detail by biochemical purification, affinity chromatography with polyclonal anti BCGF antibodies; peptide-mapping of the growth factor, followed by NH2-terminal AA sequence analysis. Further studies will then attempt to clone the gene for this molecule(s) using oligonucleotide probes, and cDNA libraries constructed from the tumor cells. (2) The receptors for the growth factor molecules on NHL-B will be identified, characterized and their regulation studied with regard to the control of tumor cell growth. (3) The genes involved in the production of autocrine BCGF-like growth factors by NHL-B will be studied using cloned probes for the natural product BCGF, usually expressed in activated T cells, to determine the relationship between the neoplastic and normal growth factors, as well as control mechanisms involved in the respective gene expressions. (4) The role of differentiation in the NHL-B will be explored to determine the cause as well as the effect of blocks in B cell differentiation on the biology of the NHL-B. These functional studies will hopefully contribute to the further development of biologic response modification (BRM) therapy for these diseases in the forseeable future.